Clonidine causes antidepressant-like effects in rats by activating α2-adrenoceptors outside the locus coeruleus

Clonidine,0.05, 0.1 and 0.5 mg/kg administered i.p. as a three-injection course but not as single doses, significantly reduced the immobility of rats in the forced swimming test. Doses of 0.1 and 0.5, administered the same way, significantly reduced activity in an open field. The effect of 0.05 and 0.5 mg/kg clonidine on immobility was prevented by 1 mg/kg idazoxan, an α₂-adrenoceptor antagonists, but not by 3 mg/kg prazosin, which blocks α₂-adrenoceptors. An infusion of 6 μg/μl 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, did not modify the effect of 0.05 and 0.5 mg/kg clonidine on immobility. Chronic treatment with 5 mg/kg i.p. desipramine or 0.1 mg/kg i.p. clonidine, twice daily for 15 days, did not modify the effect of a three-injection course with 0.1 mg/kg clonidine. It is suggested that clonidine exerts antidepressants-like effects on rats in the forced swimming test by acting on central α₂-adrenoceptors outside the locus coerlus and presumably postsynaptically to noradrenalin-containing neurons. No tolerance or sensitization of the clonidine effect was found after chronic treatment with desipramine or clonidine. These findings are of significance for these effects of clonidine in subgroups of depressed patients.